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CAMBRIDGE, MASS. & OSAKA, JAPAN--( / )--Takeda Pharmaceutical Company Limited (TSE: 4502/NYSE:TAK) today announced that the company will present data at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO), May 31-June 4 in Chicago and the 24th Congress of the European Hematology Association (EHA), June 13-16 in Amsterdam.

“We look forward to presenting data at ASCO and EHA that illustrate the continued progress of our portfolio in both clinical research and real-world settings in solid tumors and blood cancers,” said Phil Rowlands, Ph.D., Head, Oncology Therapeutic Area Unit, Takeda. “These data demonstrate our continued commitment to the discovery, development and delivery of medicines for patients with cancers.”

At ASCO, Takeda will present data from both its lung portfolio and hematology portfolio. Results from a Phase 1/2 first-in-human, open-label, multicenter study of TAK-788 will be presented orally. The ongoing study is investigating the antitumor activity and safety of TAK-788 in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors harbor epidermal growth factor receptor (EGFR) exon 20 insertion mutations. Takeda also will present three posters that demonstrate our commitment to furthering the understanding of patients with anaplastic lymphoma kinase-positive (ALK+) NSCLC treated with ALUNBRIG® (brigatinib). The Phase 3 PhALLCON trial - an ongoing efficacy study of ICLUSIG® (ponatinib) in combination with reduced-intensity chemotherapy in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) - will be featured in a poster presentation. Additional data from the ECHELON-1 and ECHELON-2 trials evaluating ADCETRIS® (brentuximab vedotin) as a frontline treatment option in patients with newly diagnosed Stage III and IV Hodgkin lymphoma and in CD30+ peripheral T-cell lymphoma, respectively, will also be shared in partnership with Seattle Genetics.

At EHA, additional analyses from the TOURMALINE-MM3 trial, which is investigating NINLARO™ (ixazomib) as a post-transplant maintenance therapy in adult patients with multiple myeloma, will be presented, including quality of life and outcomes in patients who deepened their responses while on ixazomib maintenance. Furthermore, preliminary demographics, baseline characteristics and electronic patient-reported outcomes of patients enrolled in the US MM-6 trial, a study of multiple myeloma patients who transitioned from treatment with VELCADE® (bortezomib) to treatment with NINLARO, will be presented. Real-world findings will also be featured at the meeting, including results from INSIGHT-MM, a global, prospective, non-interventional, observational study of presentation, treatment patterns and outcomes in multiple myeloma by age and geographical region. ADCETRIS will be featured in encore presentations including three-year results from the ECHELON-1 trial, which will be presented during an oral, as well as results from the ECHELON-2 trial.

The eight Takeda-sponsored abstracts accepted for presentation during ASCO 2019 and 11 abstracts at EHA 2019 include:

ASCO Annual Meeting 2019

Note: All times listed are in Central Daylight Time

TAK-788

· Antitumor Activity of TAK-788 in NSCLC with EGFR Exon 20 Insertions. Abstract 9007. Oral Presentation. Monday, June 3, 10:12 - 10:24 a.m. (Hall B1).

ALUNBRIG (brigatinib)

· Brigatinib (BRG) Versus Crizotinib (CRZ) in Asian Versus Non-Asian Patients (pts) in the Phase 3 ALTA-1L Trial. Abstract 9026. Poster Presentation. Sunday, June 2, 8 - 11 a.m. (Hall A).

· Phase 2 Study of Brigatinib in Patients (pts) with Anaplastic Lymphoma Kinase (ALK)?Positive, Advanced Non-Small Cell Lung Cancer (NSCLC) that Progressed on Alectinib or Ceritinib. Abstract TPS9115. Poster Presentation. Sunday, June 2, 8 - 11 a.m. (Hall A).

· Health-Related Quality of Life (HRQoL) Results from ALTA-1L: Phase 3 Study of Brigatinib vs Crizotinib as First-Line (1L) ALK Therapy in Advanced ALK+ Non-Small Cell Lung Cancer (NSCLC). Abstract 9084. Poster Presentation. Sunday, June 2, 8 - 11 a.m. (Hall A).

ICLUSIG (ponatinib)

· Phase 3 PhALLCON Study: Ponatinib (PON) vs Imatinib (IM) With Reduced-Intensity Chemotherapy (CT) in Patients (pts) With Newly Diagnosed Philadelphia Chromosome-Positive (Ph+) ALL. Abstract TPS7061. Poster Presentation. Monday, June 3, 8 - 11 a.m. (Hall A).

ADCETRIS (brentuximab vedotin)

· Brentuximab Vedotin with Chemotherapy for Stage 3/4 Classical Hodgkin Lymphoma: Three-Year Update of the ECHELON-1 Study. Abstract 7532. Poster Presentation. Monday, June 3, 8 - 11 a.m. (Hall A).

· Response to Brentuximab Vedotin by CD30 Expression: Results from Five Trials in PTCL, CTCL, and B-Cell Lymphomas. Abstract 7543. Poster Presentation. Monday, June 3, 8 - 11 a.m. (Hall A).

· Response to A+CHP by CD30 Expression in the ECHELON-2 Trial. Abstract 7538. Poster Presentation. Monday, June 3, 8 - 11 a.m. (Hall A).

EHA 24th Congress

Note: All times listed are in Central European Time

Multiple Myeloma / NINLARO (ixazomib)

· Deepening Responses Seen with Ixazomib Maintenance Post-Autologous Stem Cell Transplantation (ASCT) are Associated with Prolonged Progression-Free Survival - Analysis from the TOURMALINE-MM3 Study. Abstract PS1382. Poster Presentation. Saturday, June 15, 5:30 - 7:00 p.m. (Poster Area).

· Health-related Quality of Life (HRQoL) Outcomes of Oral Ixazomib Maintenance Therapy Post Autologous Stem Cell Transplant (ASCT) In Newly Diagnosed Multiple Myeloma (NDMM) from TOURMALINE-MM3. Abstract PF626. Poster Presentation. Friday, June 14, 5:30 - 7:00 p.m. (Poster Area).

· Evolving Treatment Patterns in Multiple Myeloma (MM) Differ by Age and Region: Analysis from INSIGHT-MM, A Global, Prospective, Observational Study. Abstract PF601. Poster Presentation. Friday, June 14, 5:30 - 7:00 p.m. (Poster Area).

· Long-Term Proteasome Inhibition (LTPI) in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM): US MM-6, A Real-World (RW) Study Transitioning from Bortezomib (Btz) to Ixazomib (Ixa). Abstract PF729. Poster Presentation. Friday, June 14, 5:30 - 7:00 p.m. (Poster Area).

· Comparative Effectiveness of Triplets Containing Bortezomib (B), Carfilzomib (C), Daratumumab (D), or Ixazomib (I) in Relapsed/Refractory Multiple Myeloma (RRMM) in Routine Care in the US. Abstract PS1419. Poster Presentation. Saturday, June 15, 5:30 - 7:00 p.m. (Poster Area).

· Characteristics and Treatment Outcomes of Newly Diagnosed Multiple Myeloma (NDMM) Non-Stem Cell Transplant (nSCT) Patients in the UK, Germany, and France. Abstract PS1411. Poster Presentation. Saturday, June 15, 5:30 - 7:00 p.m. (Poster Area).

· Evolving Treatment Patterns in Non-Stem Cell Transplant (nSCT) Newly Diagnosed Multiple Myeloma (NDMM): Results from a Real-World Chart Review in France, Germany, and the UK. Abstract PS1416. Poster Presentation. Saturday, June 15, 5:30 - 7:00 p.m. (Poster Area).

· Impact of Patients Characteristics on Health-Related Quality of Life in Patients with Relapsed or Refractory Multiple Myeloma: Results From The CharisMMa Study. Abstract PF615. Poster Presentation. Friday, June 14, 5:30 - 7:00 p.m. (Poster Area).

ADCETRIS (brentuximab vedotin)

· Frontline Brentuximab Vedotin with Chemotherapy for Stage 3/4 Classical Hodgkin Lymphoma: 3-Year Update of the ECHELON-1 Study. Abstract S820. Oral Presentation. Saturday, June 15, 12:00 - 12:15 p.m. (Hall 5).

· The ECHELON-2 Trial: Results of a Randomized, Double-Blind Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in Frontline Treatment of Patients with CD30+ Peripheral T-Cell Lymphomas. Abstract PS1070. Poster Presentation. Saturday, June 15, 5:30 - 7:00 p.m. (Poster Area).

· Contemporary Treatment Patterns and Response in Relapse/Refractory Cutaneous T-Cell Lymphoma (CTCL) in Clinical Practice in France, Germany, Italy, Spain and the United Kingdom. Abstract PS1256. Poster Presentation. Saturday, June 15, 5:30 - 7:00 p.m. (Poster Area).

For more information, please see ASCO () and EHA () online programs.

About ADCETRIS

ADCETRIS is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics' proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells.

ADCETRIS injection for intravenous infusion has received FDA approval for six indications in adult patients with: (1) previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression in 2017, adults with pcALCL or CD30-expressing MF who have had prior systemic therapy in 2018, and for previously untreated Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine in 2019.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) for the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy and (5) for the treatment of adult patients with previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with AVD.

ADCETRIS has received marketing authorization by regulatory authorities in more than 70 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.

ADCETRIS is being evaluated broadly in more than 70 clinical trials, including a Phase 3 study in first-line Hodgkin lymphoma (ECHELON-1) and another Phase 3 study in first-line CD30-positive peripheral T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-positive malignancies.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) Important Safety Information (European Union)

Please refer to Summary of Product Characteristics (SmPC) before prescribing.

CONTRAINDICATIONS

ADCETRIS is contraindicated for patients with hypersensitivity to brentuximab vedotin and its excipients. In addition, combined use of ADCETRIS with bleomycin causes pulmonary toxicity.

SPECIAL WARNINGS & PRECAUTIONS

Progressive multifocal leukoencephalopathy (PML): John Cunningham virus (JCV) reactivation resulting in progressive multifocal leukoencephalopathy (PML) and death can occur in patients treated with ADCETRIS. PML has been reported in patients who received ADCETRIS after receiving multiple prior chemotherapy regimens. PML is a rare demyelinating disease of the central nervous system that results from reactivation of latent JCV and is often fatal.

Closely monitor patients for new or worsening neurological, cognitive, or behavioral signs or symptoms, which may be suggestive of PML. Suggested evaluation of PML includes neurology consultation, gadolinium-enhanced magnetic resonance imaging of the brain, and cerebrospinal fluid analysis for JCV DNA by polymerase chain reaction or a brain biopsy with evidence of JCV. A negative JCV PCR does not exclude PML. Additional follow up and evaluation may be warranted if no alternative diagnosis can be established Hold dosing for any suspected case of PML and permanently discontinue ADCETRIS if a diagnosis of PML is confirmed.

Be alert to PML symptoms that the patient may not notice (e.g., cognitive, neurological, or psychiatric symptoms).

Pancreatitis: Acute pancreatitis has been observed in patients treated with ADCETRIS. Fatal outcomes have been reported. Closely monitor patients for new or worsening abdominal pain, which may be suggestive of acute pancreatitis. Patient evaluation may include physical examination, laboratory evaluation for serum amylase and serum lipase, and abdominal imaging, such as ultrasound and other appropriate diagnostic measures. Hold ADCETRIS for any suspected case of acute pancreatitis. ADCETRIS should be discontinued if a diagnosis of acute pancreatitis is confirmed.

Pulmonary Toxicity: Cases of pulmonary toxicity, some with fatal outcomes, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome (ARDS), have been reported in patients receiving ADCETRIS. Although a causal association with ADCETRIS has not been established, the risk of pulmonary toxicity cannot be ruled out. Promptly evaluate and treat new or worsening pulmonary symptoms (e.g., cough, dyspnoea) appropriately. Consider holding dosing during evaluation and until symptomatic improvement.

Serious infections and opportunistic infections: Serious infections such as pneumonia, staphylococcal bacteremia, sepsis/septic shock (including fatal outcomes), and herpes zoster, and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in patients treated with ADCETRIS. Carefully monitor patients during treatment for emergence of possible serious and opportunistic infections.

Infusion-related reactions (IRR): Immediate and delayed IRR, as well as anaphylaxis, have been reported with ADCETRIS. Carefully monitor patients during and after an infusion. If anaphylaxis occurs, immediately and permanently discontinue administration of ADCETRIS and administer appropriate medical therapy. If an IRR occurs, interrupt the infusion and institute appropriate medical management. The infusion may be restarted at a slower rate after symptom resolution. Patients who have experienced a prior IRR should be premedicated for subsequent infusions. IRRs are more frequent and more severe in patients with antibodies to ADCETRIS.

Tumor lysis syndrome (TLS): TLS has been reported with ADCETRIS. Patients with rapidly proliferating tumor and high tumor burden are at risk of TLS. Monitor these patients closely and manage according to best medical practice.

Peripheral neuropathy (PN): ADCETRIS treatment may cause PN, both sensory and motor. ADCETRIS-induced PN is typically an effect of cumulative exposure to ADCETRIS and is reversible in most cases. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Patients experiencing new or worsening PN may require a delay and a dose reduction or discontinuation of ADCETRIS.

Hematological toxicities: Grade 3 or Grade 4 anemia, thrombocytopenia, and prolonged (equal to or greater than one week) Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Monitor complete blood counts prior to administration of each dose.

Febrile neutropenia: Febrile neutropenia has been reported with ADCETRIS. Complete blood counts should be monitored prior to administration of each dose of treatment. Closely monitor patients for fever and manage according to best medical practice if febrile neutropenia develops.

When ADCETRIS is administered in combination with AVD, primary prophylaxis with G-CSF is recommended for all patients beginning with the first dose.

Stevens-Johnson syndrome (SJS): SJS and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. Fatal outcomes have been reported. Discontinue treatment with ADCETRIS if SJS or TEN occurs and administer appropriate medical therapy.

Gastrointestinal (GI) Complications: GI complications, some with fatal outcomes, including intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulcer, perforation and haemorrhage, have been reported with ADCETRIS. Promptly evaluate and treat patients if new or worsening GI symptoms occur.

Hepatotoxicity: Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been reported with ADCETRIS. Serious cases of hepatotoxicity, including fatal outcomes, have also occurred. Pre-existing liver disease, comorbidities, and concomitant medications may also increase the risk. Test liver function prior to treatment initiation and routinely monitor during treatment. Patients experiencing hepatotoxicity may require a delay, dose modification, or discontinuation of ADCETRIS.

Hyperglycemia: Hyperglycemia has been reported during trials in patients with an elevated body mass index (BMI) with or without a history of diabetes mellitus. Closely monitor serum glucose for patients who experiences an event of hyperglycemia. Administer anti-diabetic treatment as appropriate.

Renal and Hepatic Impairment: There is limited experience in patients with renal and hepatic impairment. Available data indicate that MMAE clearance might be affected by severe renal impairment, hepatic impairment, and by low serum albumin concentrations.

CD30+ CTCL: The size of the treatment effect in CD30 + CTCL subtypes other than mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL) is not clear due to lack of high level evidence. In two single arm phase II studies of ADCETRIS, disease activity has been shown in the subtypes Sezary syndrome (SS), lymphomatoid papulosis (LyP) and mixed CTCL histology. These data suggest that efficacy and safety can be extrapolated to other CTCL CD30+ subtypes. Carefully consider the benefit-risk per patient and use with caution in other CD30+ CTCL patient types.

Sodium content in excipients: This medicinal product contains 13.2 mg sodium per vial, equivalent to 0.7% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

INTERACTIONS

Patients who are receiving a strong CYP3A4 and P-gp inhibitor, concomitantly with ADCETRIS may have an increased risk of neutropenia. If neutropenia develops, refer to dosing recommendations for neutropenia (see SmPC section 4.2). Co-administration of ADCETRIS with a CYP3A4 inducer did not alter the plasma exposure of ADCETRIS, but it appeared to reduce plasma concentrations of MMAE metabolites that could be assayed. ADCETRIS is not expected to alter the exposure to drugs that are metabolized by CYP3A4 enzymes.

PREGNANCY: Advise women of childbearing potential to use two methods of effective contraception during treatment with ADCETRIS and until 6 months after treatment. There are no data from the use of ADCETRIS in pregnant women, although studies in animals have shown reproductive toxicity. Do not use ADCETRIS during pregnancy unless the benefit to the mother outweighs the potential risks to the fetus.

LACTATION (breast-feeding): There are no data as to whether ADCETRIS or its metabolites are excreted in human milk, therefore a risk to the newborn/infant cannot be excluded. With the potential risk, a decision should be made whether to discontinue breast-feeding or discontinue/abstain from therapy with ADCETRIS.

FERTILITY: In nonclinical studies, ADCETRIS treatment has resulted in testicular toxicity, and may alter male fertility. Advise men being treated with ADCETRIS not to father a child during treatment and for up to 6 months following the last dose.

Effects on ability to drive and use machines: ADCETRIS may have a moderate influence on the ability to drive and use machines.

UNDESIRABLE EFFECTS

Monotherapy: The most frequent adverse reactions (≥10%) were infections, peripheral sensory neuropathy, nausea, fatigue, diarrhoea, pyrexia, upper respiratory tract infection, neutropenia, rash, cough, vomiting, arthralgia, peripheral motor neuropathy, infusion-related reactions, pruritus, constipation, dyspnoea, weight decreased, myalgia and abdominal pain. Serious adverse drug reactions occurred in 12% of patients. The frequency of unique serious adverse drug reactions was ≤1%. Adverse events led to treatment discontinuation in 24% of patients.

Combination Therapy: In the study of ADCETRIS as combination therapy with AVD in 662 patients with previously untreated advanced HL, the most common adverse reactions (≥ 10%) were: neutropenia, nausea, constipation, vomiting, fatigue, peripheral sensory neuropathy, diarrhoea, pyrexia, alopecia, peripheral motor neuropathy, decreased weight, abdominal pain, anaemia, stomatitis, febrile neutropenia, bone pain, insomnia, decreased appetite, cough, headache, arthralgia, back pain, dyspnoea, myalgia, upper respiratory tract infection, alanine aminotransferase increased. Serious adverse reactions occurred in 36% of patients. Serious adverse reactions occurring in ≥ 3% of patients included febrile neutropenia (17%), pyrexia (6%), and neutropenia (3%). Adverse events led to treatment discontinuation in 13% of patients.

ADCETRIS (brentuximab vedotin) Important Safety Information (U.S.)

BOXED WARNING

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML): JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.

Contraindication

ADCETRIS concomitant with bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).

Warnings and Precautions

· Peripheral neuropathy (PN): ADCETRIS causes PN that is predominantly sensory. Cases of motor PN have also been reported. ADCETRIS-induced PN is cumulative. Monitor for symptoms such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. Institute dose modifications accordingly.

· Anaphylaxis and infusion reactions: Infusion-related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an IRR occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy. Premedicate patients with a prior IRR before subsequent infusions. Premedication may include acetaminophen, an antihistamine, and a corticosteroid.

· Hematologic toxicities: Fatal and serious cases of febrile neutropenia have been reported with ADCETRIS. Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS.

Administer G-CSF primary prophylaxis beginning with Cycle 1 for patients who receive ADCETRIS in combination with chemotherapy for previously untreated Stage III/IV cHL or previously untreated PTCL.

Monitor complete blood counts prior to each ADCETRIS dose. Monitor more frequently for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.

· Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in ADCETRIS-treated patients. Closely monitor patients during treatment for bacterial, fungal, or viral infections.

· Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.

· Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid use in patients with severe renal impairment.

· Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid use in patients with moderate or severe hepatic impairment.

· Hepatotoxicity: Fatal and serious cases have occurred in ADCETRIS-treated patients. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first ADCETRIS dose or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk. Monitor liver enzymes and bilirubin. Patients with new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.

· PML: Fatal cases of JC virus infection resulting in PML have been reported in ADCETRIS-treated patients. First onset of symptoms occurred at various times from initiation of ADCETRIS, with some cases occurring within 3 months of initial exposure. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider PML diagnosis in patients with new-onset signs and symptoms of central nervous system abnormalities. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.

· Pulmonary toxicity: Fatal and serious events of noninfectious pulmonary toxicity, including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome, have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In the event of new or worsening pulmonary symptoms, hold ADCETRIS dosing during evaluation and until symptomatic improvement.

· Serious dermatologic reactions: Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.

· Gastrointestinal (GI) complications: Fatal and serious cases of acute pancreatitis have been reported. Other fatal and serious GI complications include perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus. Lymphoma with preexisting GI involvement may increase the risk of perforation. In the event of new or worsening GI symptoms, including severe abdominal pain, perform a prompt diagnostic evaluation and treat appropriately.

· Embryo-fetal toxicity: Based on the mechanism of action and animal studies, ADCETRIS can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus, and to avoid pregnancy during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.

Most Common (≥20% in any study) Adverse Reactions

Peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia, and mucositis.

Drug Interactions

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View source version 백운역홀덤펍 검정스타킹 on businesswire.com:doola Launches Banking Product for Global Businesses, Allowing Founders Worldwide to Launch 백운역홀덤펍 라이브자스민 an LLC, DAO LLC, or C Corp and Remotely Open a 스포츠중계아이언TV 온라인채팅 US Bank Account, All In 백운역홀덤펍 섹시한 One Go